Wyoming Research Innovations, Inc. will develop in situ cross-linkable hydrogels, called synthetic extracellular matrix (sECM), for soft tissue repair. The ability to fill a traumatic, surgical, or chronic defect with a self-molding cell-interactive sECM prepared with a fast-curing mixture of biocompatible macromonomers would have significant clinical utility. These materials will be prepared from chemically modified hyaluronic acid and chondroitin sulfate, which are two major glycosaminoglycan (GAG) components of the ECM. Biomaterials from cross-linked GAG derivatives produce versatile new bioinspired materials. The sECM concept incorporates ECM proteins as well as GAGs, and we propose to demonstrate that crosslinking can occur in the presence of seeded cells and in a tissue defect in vivo. Two crosslinking chemistries will be investigated and the resulting materials will be evaluated for compatibility with cell growth. In situ cross-linked materials will be evaluated for in vivo efficacy in an animal model. The proposed materials address an unmet need in surgical care and wound repair. Many surgical defects, traumatic wounds and deep chronic wounds fail to heal without augmentation using grafted natural or synthetic materials. A biocompatible hydrogel that mimics ECM and is conducive to cell seeding and growth would have many important clinical applications.